The shifting paradigms of Diet and Cancer
Jacob Schor ND, FABNO
September 7, 2015
NOTE: Once again this topic is on the tedious side, a summary of various scientific ideas over the past half century related to diet and cancer risk.
Over the past fifty years scientific belief as to how diet might impact cancer risk has undergone a number of dramatic shifts, moving (some would say evolving) from one worldview to another with such regularity that a close examination of these changing ideas may be useful to not only inform our understanding of what to eat (or not to eat) but also to illustrate how much scientific ‘truth’ shifts over time and to illustrate how we may need to be flexible in interpreting ‘facts’. 
Back in the 1950s and 1960s, scientific suspicion focused on things in food, mostly things added to foods, as the cause of cancer. First to be blamed were chemicals added to foods , the preservatives , food colorings , nitrates , pesticide residues  and smoke flavorings : food itself was not thought to impact disease, rather it was the additions to food that were the problem.
In the 1960s, the blame shifted slightly to the idea that, perhaps food itself could be carcinogenic; the high temperature grilling of meat became the prime suspect. Cooked meat  and heated fats  were the new cause of cancer; a burger and fries had to be avoided to stay cancer free. Coffee was thought to cause kidney cancer, and nuts were a danger because they might contain aflatoxins.  Broiled meat was the source of benzopyrenes, heterocyclic amines and polycyclic hydrocarbons, chemicals that certainly sounded like they were dangerous. 
The once strong association between cooked meat and cancer, in particular colon cancer, has grown weaker over time. For example, Kampman et al wrote in a 1999 paper, “The frequency of fried, broiled, baked, or barbecued meat, use of drippings, and doneness of meat were not significantly associated with risk.”  Heterocyclic amines may still increase risk, but less so than once thought. Cooked meat is not the cause of all cancer.
While science has by and large dropped this ‘additive’ theory, the idea persists strongly. Many people chose to avoid foods with additives, especially preservatives, out of fear consumption will cause cancer.
There is a near universal belief that consuming organic food, produced without pesticides and processed without chemical additives, will lower risk of cancer. Those of us who routinely see cancer patients are often asked, “How can I have cancer? I only eat organic food!”
Organic food is appealing for a number of social and ecologic reasons but it isn’t clear that people who eat it will significantly improve health. A 2012 meta-analysis of 17 human studies and 223 studies of nutrient and contaminant levels in food concluded that, “The published literature lacks strong evidence that organic foods are significantly more nutritious than conventional foods.” 
Exposure to pesticides in large quantities, as in the farm workers who apply them, is linked to higher risk of certain cancers, in particular non-Hodgkin lymphoma, soft tissue sarcoma and breast cancer. [13, 14] yet there isn’t much evidence that eating organic foods does much to lower risk of cancer.
A 2014 paper in the British Journal of Cancer reports that in a large prospective study that followed 623, 080 middle-aged U.K. women for 9.3 years, that the reported cases of cancer (n=53, 769 cases) did not differ significantly by the amount of organic foods the women reported eating. Actually risk for breast cancer was slightly higher in those reporting that they always or usually chose organics (breast cancer (RR=1.09, 95% CI: 1.02-1.15),) (a finding we want to ignore as it clashes with our view of the world). Non-Hodgkin lymphoma was about 21% lower in the organic eaters.  Otherwise there were no significant differences.
By the way, sales of organic food in the U.K. have grown from £100 million/ year in 1994 to £2 billion in 2008. In the US the jump is staggering: organic sales have gone from under $4 billion/ year in 1997 to over $39.1 billion in 2014.  Despite the lack of strong evidence of a health benefit, people remain strongly drawn to the idea that our food is to blame for cancer.
This idea that chemicals in foods caused all cancer, to quote Dr. Walter Willet of Harvard School of Public Health, “… was the first paradigm.” Willet sees our understanding of how diet affects cancer as slowly evolving from one principle culprit to another, or as he sees it from one paradigm to another.
In Willet’s view the second paradigm of cancer causes “… was the idea that fat in the diet is a major cause of cancer.” 
Fat was in both scientific and popular belief, the culprit, the cause of cancer. The highest goal of dietary counseling a quarter century ago, was to achieve and maintain a low fat diet.  Clinical trials of low fat, high carbohydrate diets were undertaken to prevent diseases ranging from breast cancer  to actinic keratosis.  Yet, in Willet’s words,
“There was never any strong evidence for this idea, but it was repeated so often that it became dogma in the 1980s and 1990s. For conditions such as heart disease and diabetes, the type of fat in the diet is quite important. But the hypothesis that the percentage of calories from fat in the diet is an important determinant of cancer risk, at least during midlife and later, is not supported by the data.”
In a 2004 PBS Frontline interview, when asked whether low fat diets have made us fat, Willet famously answered, “This campaign to reduce fat in the diet has had some pretty disastrous consequences. ... One of the most unfortunate unintended consequences of the fat-free crusade was the idea that if it wasn't fat, it wouldn't make you fat. I even had colleagues who were telling the public that you can't get fat eating carbohydrates. Actually, farmers have known for thousands of years that you can make animals fat by feeding them grains, as long as you don't let them run around too much, and it turns out that applies to humans. We can very easily get fat from eating too many carbohydrates, and the public was really directed to only focus on fat calories, when we really have to keep an eye on calories no matter where they're coming from.” http://www.pbs.org/wgbh/pages/frontline/shows/diet/themes/lowfat.html
“The third paradigm” according to Willet, “was that fruits and vegetables dramatically reduce risks of cancer.” Along with this we could include the idea that certain nutrients found in these foods would provide ample protection. Instead of things added to foods being the problem, it was deficiency of some of the chemicals found in foods that was to blame for cancer. We needed more of these chemical, things like antioxidants or phyto-nutrients, minerals or enzymes.
Recall the famous CARET and WHEL trials that failed so miserably, studies that were based on the notion that we understood what was missing from the diet, things that we could either take out or add back in that would stop cancer.
The Β-Carotene and Retinol Efficacy Trial (CARET) was such a surprising failure, it should be taught in naturopathic school as a lesson in humility and as a cautionary warning about leaping to conclusions based on epidemiological evidence. Recall that the trial followed 18,314 study participants, who, because of heavy smoking, were at high risk for lung cancer. Recall also that the study was halted far earlier than planned, back in 1996, because the participants taking beta-carotene supplements had a 28% increase in lung cancer incidence and a 17% increase in death compared to the placebo group. The study participants who had taken beta-carotene remained at higher risk than the placebo group even five years after stopping supplementation.  It was not supposed to work this way.
The Women’s Healthy Eating and Living (WHEL) Trial on breast cancer recurrence started recruiting women in 1995 and followed them to 2006, during the transition from the ‘fat paradigm’ to the ‘phyto-nutrient deficiency paradigm’. Of the 3,088 women recruited, all of whom had been diagnosed and treated for breast cancer, 1,537 were assigned to a combination low fat and high vegetable and fruit diet. During a mean 7.3-years follow up, recurrence of, new primary invasive breast cancer diagnosis, or death in the two groups was tracked. In the end, 16.7% of the women in the intervention group and 16.9% in the control group experienced an event, that is cancer occurrence, recurrence or death. These differences are not significantly different. In simple words, the extreme dietary interventions based on both the low fat and high phytonutrient theories had no measurable impact on what mattered most, cancer. 
While some trials have demonstrated positive results, the overall benefits of adding food nutrients via the diet have been less than we had hoped for.
In Willet’s words, “That's not to say there's no benefit from fruits and vegetables, but [the benefit is] probably very small and limited to certain foods and certain cancers.”
We have now emerged into what Willet describes as the fourth paradigm: “…. that a major cause of cancer is excessive adiposity [obesity].” Talking about weight is a tricky subject these days, filled with politically correct terminology; obesity is now euphemistically described as a “positive energy balance.” In simpler terms, the theory is that too many people are too fat. Not just too fat but because they expend too few calories as a result of inactivity, they are insulin resistant and so produce excessive amounts of insulin hormone. Current thinking is that because insulin may bind to some IGF-1 receptor sites, it acts as a growth factor for many types of cancer cells.
I frequently describe a Danish study (Skuladottir et al, 2006) to patients as an illustration of the relative impact of fruits and vegetables compared to dietary starch on cancer. This study examined diet and lung cancer survival times and is helpful to illustrate our new focus on energy balance, blood sugar and insulin.
The Danes followed a large cohort, 57,053 subjects, and reported that those with the highest intake of fruit and vegetables had a lower risk of dying, while the people with the highest intakes of potatoes had an increased risk of dying. High intake of vegetables decreased risk of dying by 16%, and of fruit by 19%, but high intake of potatoes increased risk of death by 51%.  Potatoes have a very high glycemic index. Harvard’s Glycemic Index of Foods, as impossible as it sounds, lists baked potatoes as raising blood sugar levels more than eating pure glucose. 
Evidence that supporting these ‘new’ ideas regarding energy balance and cancer was there a quarter century ago  yet seems to have been ignored because it didn’t fit the working paradigm of the time.
This current positive energy balance paradigm, in Willet’s opinion is here to stay, at least for the time being as the evidence seems more consistent than earlier theories.
High glycemic load is associated with greater risk for colon cancer recurrence. A 2012 paper reported that in stage III colon cancer patients, those consuming the most blood sugar raising carbohydrates in their diet had a nearly 80% higher risk of recurrence than those patients consuming the least. [highest quintile of dietary glycemic load vs. lowest quintile: HR 1.79 for disease-free survival]. 
Willet’s current assessment is that obesity is the most important dietary culprit, “On a population level, the number of cases of cancer attributable to people being overweight and obese is about equal to the number attributable to current smoking. This is in part because smoking is going down and obesity is going up; in terms of importance within a population, they are in the same ballpark. …..”
Yet there are already holes developing in the new paradigm.
The ‘obesity/hyperinsulinemia effect’ may not be as large as the researchers want us to believe. A March 2015 meta-analysis of prospective cohort studies looked at data on dietary patterns and risk of breast cancer and reported,
“…A dietary pattern with a high glycemic index was associated with a summary relative risk (SRR) of 1.05 … and a high glycemic load with a SRR of 1.06 ….” While these effects are statistically significant but they are minor. 
Once again the paradigm of the day may not be as permanent as we first hoped.
Perhaps we have been going about this the wrong way. We have been seeking both a cause for and a cure for cancer as if there will be a simple straight-forward answer, as if cancer was a disease like scurvy.
[Scurvy as everyone now knows is caused by vitamin C deficiency. This is a simple cause and effect relationship and easy to understand, yet even so for hundreds of years, people, in particular sailors, died from the disease. Scottish surgeon James Lind is credited with reporting the cure for scurvy in 1753. The fact that it wasn’t until 1867 that the British Navy began to supply daily rations of lime juice to sailors  is often used to illustrate how slow it takes medicine or society to incorporate advances in science into common practice.]
There are two lessons we must learn. The first is that cancer generally defies simple explanations.
We keep looking to find the Vitamin C that will prevent or cure cancer. It is time to face the fact that this disease is in most cases multi-factorial, that there are many different factors that interact and together trigger cancer. It’s not scurvy. For the majority of cancers there are no simple solutions.
Admittedly in the few where there are clear solutions, yet we hesitate to act forcefully; take lung cancer and smoking for example. Smoking is responsible for about 140,000 lung cancer deaths in the U.S. each year. One might think this would provoke a strong reaction on par with our efforts to invest in eating organic foods but this clear threat hasn’t stopped people from smoking. Government data tell us that 17.8% of all adults in the US smoke (42.1 million people)  This is the elephant in the room, so to speak, so let’s take a moment to acknowledge the facts:
“Cigarette smoking is responsible for more than 480,000 deaths per year in the United States, including nearly 42,000 deaths resulting from secondhand smoke exposure. This is about one in five deaths annually, or 1,300 deaths every day.”  This brings us to what may be the greatest oxymoron of all times, the organic food eating smoker.
We also have to face the fact that identifying and removing one of these factors does not necessarily cure the disease. It’s usually more complicated.
Some of the explanations for cancer are true some of the time, for some cancers, but they can’t be applied generally. For example, just because H. pylori infections are strongly associated with gastric cancer , does not mean H. pylori causes all cancers or that eradicating these infections will prevent more than a narrow group of cancers.
Some of the explanations that we thought true years ago have turned out to be of less significance than originally thought, or in some cases, like fat, not to blame at all. It’s easy to get set in our ways, to think that we learned years ago, is an enduring truth. Inherited beliefs that have been proven to have no merit are often termed superstition, a term that is perhaps too strong, but perhaps some of these past paradigm ideas that are no longer accepted might be called “Old Scientist’s Tales?”
Lots of ideas have waxed then waned over the years. Some have decreased in importance while others have grown. If we truly want to prevent cancer we need to keep our minds open and adjust what we do and how we eat as the science and the evidence shifts. What we thought was true a few years back is not necessarily true today.
NOTES and REFERENCES:
1. Note: many of the thoughts in this article come from a brilliant lecture given by Walter Willet several years ago at a conference sponsored by the National Cancer Institute at their 2012 annual conference on advances in cancer prevention: http://videocast.nih.gov/summary.asp?Live=11425&bhcp=1
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